液相色谱-质谱联用法测定参蛇软膏中雷公藤甲素的含量

摘 要 目的：建立一种液相色谱 质谱联用法测定参蛇软膏中雷公藤甲素的含量。方法: 色谱条件：色谱柱为Agilent TC C18柱（250 mm×4.6 mm,5 μm）,流动相为甲醇-0.1%甲酸水溶液（73∶27,v/v）,流速为0.5 ml·min^-1,柱温为35℃,进样量为2 μl;质谱条件：采用电喷雾离子源(ESI),多反应离子监测（MRM）,正离子检测模式,以甲硝唑为内标,检测雷公藤甲素;监测离子：雷公藤甲素m/z 361.4→43.2,甲硝唑m/z 172.1→128.0。结果: 雷公藤甲素在10～500 ng·mL^-1范围内呈良好的线性关系,r=0.999 9;定量限（LOQ）为9.5 ng·mL^-1;日内和日间精密度（RSD）均小于3%,平均回收率为96.87%（RSD=2.79,n=6）。结论:本方法简单、快速、灵敏、准确,可用于参蛇软膏中雷公藤甲素的含量测定。     

GC-MS法测定奥拉西坦原料中的潜在遗传毒性杂质

摘 要 目的：建立同时测定奥拉西坦原料药中潜在遗传毒性杂质氯乙酸甲酯和(R,S)4 氯 3 羟基丁酸乙酯的方法。方法: 采用GC-MS法,使用乙酸乙酯进行提取。色谱柱为VF 1701 ms毛细管柱（30 m×0.25 mm,0.25 μm）,柱温采用程序升温,进样口温度为220℃,柱流量为1.0 ml·min^-1,吹扫流量为5.0 ml·min^-1,进样方式为分流进样,分流比为5∶1,载气为高纯氦气,检测器为MS检测器,离子源温度为230℃,接口温度为230℃,溶剂延迟时间为4 min,离子化模式为电子轰击离子化模式,扫描（检测）方式为选择性离子检测,电子能量为70 eV,进样量为1.0 μl。结果:2种杂质成分之间的分离度符合要求,浓度线性范围均为50～400 ng·mL^-1（r≥0.999 5）,加样回收率分别为89.7%～96.3%（RSD=2.3%,n=9）、91.0%～105.3%（RSD=4.4%,n=9）。结论:该方法简便、准确、灵敏、迅速,可用于奥拉西坦原料药中2种潜在遗传毒性杂质的测定。     

LC-MS/MS法测定瑞戈非尼中4-(4-氨基-3-氟苯氧基)-N-甲基吡啶-2-甲酰胺

摘 要 目的：建立抗癌新药瑞戈非尼中遗传毒性杂质4-(4-氨基-3-氟苯氧基)-N-甲基吡啶-2-甲酰胺（AFP-PMA）的含量测定方法。方法: 采用LC MS/MS法测定;利用Waters XBridge Shield RP18色谱柱（150 mm×3.0 mm,3.5 μm）进行分离,以5 mmol·L^-1乙酸铵溶液（A）-乙腈（B）为流动相,采用梯度洗脱（0~9 min,5% B→90% B）,流速为1.0 ml·min^-1,柱温50 ℃;ESI离子源,正离子扫描方式,多反应监测（MRM）模式扫描,检测离子通道为m/z262.2→244.1。结果: AFP-PMA 浓度在2.41～980.90 ng·ml^-1范围内与峰面积呈良好线性关系（r=0.999 8）;定量限为8.02 ng·ml^-1;检出限为2.41 ng·ml^-1,约为供试品溶液浓度的0.000 241%;平均加样回收率为100.95%,RSD为2.37%（n=9）。结论:本方法专属性强、灵敏度高、准确度好,可用于瑞戈非尼中4-(4-氨基3-氟苯氧基)N-甲基吡啶-2甲酰胺的含量测定。     

QuEChERS-GC-MS/MS测定蚓激酶原料药中41种农药残留量

摘 要 目的：建立QuEChERS (quick, easy, cheap, effective, rugged and safe)快速样品前处理技术结合气相色谱串联质谱法(GC-MS/MS)同时测定蚓激酶原料药中41种农药残留的方法。 方法: 采用GC-MS/MS法测定蚓激酶原料药中41种农药残留量。色谱柱为HP 5ms ultla Lert弹性石英毛细管柱（30.0 m×0.25 mm,0.25 μm）,检测器为质谱检测器,进样口温度为240℃;检测器温度为280℃,程序升温,载气为高纯氦气,隔垫吹扫为5 ml· min-1,柱流速为2.0 ml·min-1,进样量为1.0 μl,进样方式为不分流。质谱检测器离子源为电子轰击离子源,离子源温度为230℃,碰撞气为高纯氩气,灯丝电压为70 eV,传输线温度为280℃,积分延时为4 min。 结果: 41种农药检测质量浓度线性范围均为100～500 μg·L-1（r≥0.995 0）;检测限为1.5～3.8 μg·L-1;定量限为5.0~12.5 μg·L-1;精密度的RSD均<8%（n=6）、重复性与稳定性试验的RSD均<6%(n=6);蚓激酶原料药样品加样平均回收率均为70.47%～105.66%。 结论: 该方法简便、准确、高效,可用于判断蚓激酶原料药是否有农药残留。     

液相色谱电喷雾串联质谱同时测定复方甘草片中吗啡与磷酸可待因

摘 要 目的：建立复方甘草片中吗啡与磷酸可待因的含量测定方法。方法: 液相色谱电喷雾串联质谱仪,采集方式MRM（多反应监测）,色谱柱Zorbax Eclipse SB C18(2.1 mm×100 mm,3.5 μm),流动相:乙腈 15 mmol·L^-1乙酸铵,梯度洗脱。结果: 吗啡与可待因的母离子质核比分别为286.0、300.0,定量离子为165.0、165.0,吗啡在25～500 ng·ml^-1范围内线性良好,r=0.999 5,平均回收率为103.1%,磷酸可待因在0.75～150 ng·ml^-1范围内线性良好,r=0.999 5 ,平均回收率为101.5%,RSD=1.7%（n=6）。 结论:本方法灵敏度高,前处理简单,可用于复方甘草片的质量控制。     

离子色谱法测定枸橼酸氢钾钠颗粒中多种成分的含量

摘 要 目的：建立离子色谱法测定枸橼酸氢钾钠颗粒中钠、钾和枸橼酸含量的方法。方法: 钾和钠的色谱条件：采用Dionex IonPac CS12A色谱柱（250 mm×4.6 mm,5 μm）,流动相为0.02 mol·L^-1甲烷磺酸溶液,流速为1.0 ml·min^-1,抑制器为CSRS 300,抑制电流为59 mA,采用抑制型电导检测器,进样量为25 μl。枸橼酸的色谱条件：采用Dionex HPICE AS1离子排斥色谱柱（250 mm×9.0 mm,7.5 μm）,流动相为0.015 mol·L^-1硫酸溶液,流速为0.6 ml·min^-1,检测波长为220 nm,进样量为10 μl。结果: 钠的线性范围为0.82～82.49 μg·ml^-1（r=0.999 9）,平均回收率为98.9%,RSD为0.55% （n=9）;钾的线性范围为1.38～137.89 μg·ml^-1（r=1.000 0）,平均回收率为100.5%,RSD为0.53%（n=9）;枸橼酸的线性范围为0.021～10.600 mg·ml^-1（r=1.000 0）,平均回收率为99.1%,RSD为0.54%（n=9）。结论:本方法简便、快速、准确,可用于枸橼酸氢钾钠颗粒的质量控制。     

HPLC-MS/MS法测定大鼠血浆中长春花碱的浓度及药动学研究

摘 要 目的： 建立HPLC MS/MS法测定大鼠血浆中长春花碱的浓度。方法: 血浆样本加入适量内标,经乙腈直接沉淀蛋白后采用HPLC MS/MS进行分析。色谱柱采用Ultimate C18柱 (150 mm×2.1 mm,5.0 μm);流动相由乙腈 10 mmol·L^-1醋酸铵(含0.1%甲酸) (49:51)组成,柱温40℃;流速0.3 ml·min^-1;采用电喷雾离子源(ESI),以多反应监测方式(MRM)进行定量分析。长春花碱和内标长春新碱在正离子模式下定量分析离子对分别为m/z 811.4→m/z 224.2和m/z 825.4→m/z 807.4。结果: 长春花碱在0.475~ 950 ng·ml^-1内线性关系良好（r=0.997 1）,最低定量限为0.475 ng·ml^-1,提取回收率为89.15%~95.28%,日内、日间精密度RSD均不高于7.95%。药动学研究结果表明,长春花碱在大鼠体内的t1/2为（5.86 ±2.37）h,AUC(0-t)和AUC(0-∞)分别为（68.45±14.51）,（95.03±33.09）μg·L^-1·h。 结论:该方法分析速度快、灵敏、准确,为临床进一步研究长春花碱和药物转运体提供了基础。长春花碱在大鼠体内的浓度较低,半衰期较长。     

GC法测定阿魏酸哌嗪中的残留溶剂

摘 要 目的：建立阿魏酸哌嗪中苯、氯乙醇与吡啶等残留溶剂的测定方法。 方法: 采用GC法,以DB 624（30 m×0.53 mm, 1.0 μm）弹性石英毛细管柱为色谱柱,载气为氮气,采用氢火焰离子化检测器;起始温度为50℃,维持5 min,以10℃·min^-1的速率升温至80℃,再以50℃·min^-1的速率升温至200℃,维持4 min;进样口温度为200℃,检测器温度为220℃;分流比为1∶1;进样量为1 μl;柱流速为3 ml·min^-1。结果: 苯在0.16～0.96 μg·mL^-1的浓度范围内线性关系良好（r=0.999 5）,平均回收率为95.7%（RSD=2.1,n=9）,检测限为0.16 ng;氯乙醇在16.11～96.65 μg·mL^-1的浓度范围内线性关系良好（r=0.999 7）,平均回收率为97.8%（RSD=2.1,n=9）,检测限为0.62 ng;吡啶在15.87～95.23 μg·mL^-1的浓度范围内线性关系良好（r=0.999 8）,平均回收率为99.2%（RSD=1.3,n=9）,检测限为0.15 ng。结论:本测定方法可靠、简便、结果准确、稳定性好,适用于本品残留溶剂的测定。     

HPLC-CAD法同时测定硫酸卡那霉素注射液中卡那霉素和卡那霉素B的含量

摘 要 目的：建立HPLC CAD法测定硫酸卡那霉素注射液中卡那霉素和卡那霉素B含量的方法。方法: 采用Boston Green ODS C18（250 mm×4.6 mm,5 μm）色谱柱,以0.2 mol·L-1三氟醋酸溶液 甲醇（95 ∶〖KG-*2〗5）作为流动相,流速:1.0 ml·min^-1,柱温:30℃,喷雾温度:55℃,喷雾压力:56.4 psi。结果:卡那霉素在0.385~38.500 μg·ml^-1之间呈现良好的线性关系（r=0.999 9）,检出限为0.075μg·ml^-1,定量限为0.154 μg·ml^-1,回收率为100.97%（n=9）。卡那霉素B在0.374~37.400 μg·ml^-1之间呈现良好的线性关系（r=1.000 0）,检出限为0.075 μg·ml^-1,定量限为0.150 μg·ml^-1,回收率为100.44%（n=9）。结论:建立的HPLC CAD测定卡那霉素和卡那霉素B含量的方法检出限低,操作简单准确,可以有效控制硫酸卡那霉素注射液的质量。     

HPLC法测定小儿咳喘灵口服液中山梨酸钾的含量

摘 要 目的：建立HPLC法测定小儿咳喘灵口服液中防腐剂山梨酸钾的含量。方法: 采用Phenomenex Gemini C18（250 mm×4.6 mm,5 μm）色谱柱,以0.02 mol·L^-1磷酸二氢钠溶液（用磷酸调pH至4.0） 乙腈（80∶20）为流动相,流速为1.0 ml·min^-1,检测波长为262 nm,柱温为30℃,进样体积为20 μl。结果:山梨酸钾浓度在8.584～85.840 μg · mL^-1范围内与峰面积呈良好线性关系(r=0.999 9),平均回收率为100.0%,RSD为0.47%（n=9）,山梨酸钾检测限为0.43 ng,定量限为1.29 ng。结论:经过方法学验证,本法可用于小儿咳喘灵口服液中防腐剂山梨酸钾的含量测定。     

LC—MS／MS法测定人血浆中地氯雷他定及其代谢产物3-羟基地氯雷他定的浓度

目的:建立 LC-MS/MS 法测定人血浆中地氯雷他定及其主要代谢产物3-羟基地氯雷他定的浓度。方法:血浆样品经碱化后用乙醚提取,采用液相色谱-质谱联用法检测。色谱条件为分析柱 CAPCELL PAK C_(18)(50 mm×2.0 mm,5 μm),预柱Octadecyl C_(18)(4.0 mm×3.0 mm);流动相:甲醇-乙腈-5 mmol·L~(-1)甲酸铵水溶液(30:20:50);流速0.2 mL·min~(-1);柱温40℃;进样量10 μL。质谱条件为电喷雾离子源(ESI),正离子扫描;选择性监测质荷比(m/z)为311.1/259.1(地氯雷他定),327.1/275.1(3-羟基地氯雷他定),315.1/263.1(D_4-地氯雷他定,内标),331.1/279.1(D_4-3-羟基地氯雷他定,内标)带正电荷的分子离子峰。结果:地氯雷他定、3-羟基地氯雷他定的线性范围均为0.05～10.0 ng·mL~(-1),定量下限均为0.05 ng·mL~(-1),批内、批间 RSD 均小于10%。结论:该方法简便,灵敏度高,专属性强,可用于地氯雷他定及其代谢产物的临床药动学和生物等效性研究。     

LC/MS/MS与GC/MS法分析鉴定小鼠尿中沙美特罗的代谢产物

目的:鉴定沙美特罗在小鼠尿中的主要代谢产物.方法:ig给药后,收集小鼠尿液,经固相提取,葡萄糖醛酸酶水解,进行LC/MS/MS分析和硅烷化后进行GC/MS分析同时分离鉴定沙美特罗代谢产物.结果和结论:在给药后尿样中发现沙美特罗原型和4种代谢产物M1～M4,其结构推测为19-羟基沙美特罗(M1)、2-羰基沙美特罗(M2)、19-羰基沙美特罗(M3)和19-羟基-8-甲氧基沙美特罗(M4).     

LC/MS/MS的多反应监测方法定量测定灯盏乙素

目的：建立一种可靠的灯盏乙素定量分析方法。方法：用三级四极串联质谱(MS/MS)作为HPLC的检测器,其中MS/MS使用了多反应监测(MRM)扫描方式。选择母→子离子对m/z -461→m/z -285作为MRM监测的离子对;HPLC流动相为100％甲醇,流速0.9 mL.min^-1,色谱柱Beckman ODS-1。以测定短葶飞蓬提取物的灯盏乙素含量为例,对此方法进行了应用。结果：灯盏乙素在短葶飞蓬提取物中含量为6.98%。方法线性范围20～160 ng.mL^-1 (γ=0.999);加入灯盏乙素标准品20,60和160 ng的加样回收率分别为：96.5%,97.4%和97.3%。检测限为1 ng,每个样品的分析时间为4 min。结论：此法灵敏、快速、准确,可应用于灯盏乙素的各种药剂、药代的研究。     

Determination of a selection of synthetic cannabinoids and metabolites in urine by UHPSFC‐MS/MS and by UHPLC‐MS/MS

Two different analytical techniques, ultra‐high performance supercritical fluid chromatography‐tandem mass spectrometry (UHPSFC‐MS/MS) and reversed phase ultra‐high performance liquid chromatography‐tandem mass spectrometry (UHPLC‐MS/MS), were used for the determination of two synthetic cannabinoids and eleven metabolites in urine; AM‐2201 N‐4‐OH‐pentyl, AM‐2233, JWH‐018 N‐5‐OH‐pentyl, JWH‐018 N‐pentanoic acid, JWH‐073 N‐4‐OH‐butyl, JWH‐073 N‐butanoic acid, JWH‐122 N‐5‐OH‐pentyl, MAM‐2201, MAM‐2201 N‐4‐OH‐pentyl, RCS‐4 N‐5‐OH‐pentyl, UR‐144 degradant N‐pentanoic acid, UR‐144 N‐4‐OH‐pentyl, and UR‐144 N‐pentanoic acid. Sample preparation included a liquid‐liquid extraction after deconjugation with ß‐glucuronidase. The UHPSFC‐MS/MS method used an Acquity UPC^{2 TM} BEH column with a mobile phase consisting of CO₂ and 0.3% ammonia in methanol, while the UHPLC‐MS/MS method used an Acquity UPLC® BEH C₁₈ column with a mobile phase consisting of 5 mM ammonium formate (pH 10.2) and methanol. MS/MS detection was performed with positive electrospray ionization and two multiple reaction monitoring transitions. Deuterated internal standards were used for six of the compounds. Limits of quantification (LOQs) were between 0.04 and 0.4 µg/L. Between‐day relative standard deviations at concentrations ≥ LOQ were ≤20%, with biases within ±19%. Recoveries ranged from 40 to 90%. Corrected matrix effects were within 100 ± 10%, except for MAM‐2201 with UHPSFC‐MS/MS, and for UR‐144 N‐pentanoic acid and MAM‐2201 N‐4‐OH‐pentyl with UHPLC‐MS/MS. Elution order obtained by UHPSFC‐MS/MS was almost opposite to that obtained by UHPLC‐MS/MS, making this instrument setup an interesting combination for screening and confirmation analyses in forensic cases. The UHPLC‐MS/MS method has, since August 2014, been successfully used for confirmation of synthetic cannabinoids in urine samples revealing a positive immunoassay screening result. Copyright © 2015 John Wiley & Sons, Ltd.     

Simultaneous determination of desloratadine and its active metabolite 3-hydroxydesloratadine in human plasma by LC/MS/MS and its application to pharmacokinetics and bioequivalence

A rapid and simple liquid chromatographic-tandem mass spectrometric (LC/MS/MS) method was developed and validated for the simultaneous determination of desloratadine and its active metabolite 3-hydroxydesloratadine concentrations in human plasma. After liquid-liquid extraction with ethyl ether for sample preparation, the chromatographic separation was achieved on a CAPCELL PAK C18 column (50 mm x 2.0mm, 5 microm, Shiseido). [(2)H(4)]desloratadine and [(2)H(4)]3-OH desloratadine were used as internal standards. A mobile phase consisted of 5mM ammonium formate in water, methanol and acetonitrile (50:30:20). Detection was by positive ion electrospray tandem mass spectrometry on a Sciex API3000. A quadratic regression (weighted 1/concentration) gave the best fit for calibration curves over the concentration range 0.05-10 ng/mL for both desloratadine and 3-OH desloratadine. The method was shown to be accurate, rapid and sufficiently sensitive to be successfully applied to a pharmacokinetic and bioequivalent study.     

高效液相色谱-质谱联用测定人血浆中辛伐他汀浓度

目的建立测定人血浆中辛伐他汀浓度的方法。方法血浆样品中加入内标,用乙醚提取,浓缩后采用高效液相色谱-质谱联用进行测定。结果血浆样品中辛伐他汀线性范围为0.1～20ng·mL-1(r=0.9999);萃取回收率为94.3%。结论本方法灵敏度高、专属性强、重现性好、准确,可用于辛伐他汀片人体药动学及生物等效性研究。     

HPLC/MS/MS联用技术测定全血中的瑞芬太尼

目的:建立全血中瑞芬太尼的HPLC／MS／MS测定方法,并测定围麻醉期患者体内瑞芬太尼的血药浓度。方法:全血样品中加入枸橼酸芬太尼作内标,用1-氯丁烷进行提取。以乙腈与三氯甲烷(V乙腈:V三氧甲烷= 1:1)混合液加乙酸铵(2 mmol·L-1)为流动相,色谱柱为Intersil ODS-3(50 mm×2．1 mm,3μm),流速0．3 mL·min-1。三级四极杆质谱采用正离子模式,离子采集方式为多反应监测模式(MRM),离子源温度200℃,离子源电离电压为5 000 V,雾化气流速8 L·min-1。采集离子(母离子／子离子)为瑞芬太尼377／228,芬太尼337／188。结果:瑞芬太尼在0．5～50．0 ng·mL-1浓度范围内呈良好的线性(r=0．9994)。日内、日间精密度均在15％以内,提取回收率大于67．3％,方法回收率在95．0％～97．6％。结论:本方法灵敏、准确,适合瑞芬太尼的体内分析。     

System suitability in bioanalytical LC/MS/MS

System suitability is widely recognized as a critical component of bioanalysis. This paper discusses a generic system suitability test that monitors instrument performance throughout a run when used for liquid chromatography tandem mass spectrometry (LC/MS/MS) in bioanalysis. This system suitability process is designed to ensure that the LC/MS/MS system is performing in a manner that leads to the production of accurate and reproducible data that can be submitted with confidence to regulatory agencies. This process contains tests for signal stability, carryover, and instrument response. This approach is integrated throughout an analytical run and has been used in the analysis of over 25,000 batches of clinical samples. Two case studies are presented in which quality control samples and standards meet all acceptance criteria (based on Standard Operating Procedures and the Food and Drug Administration's recommendations for bioanalytical method validation) but failed the proposed system suitability test, and thus were rejected. In these case studies, the concentrations of a significant number of clinical samples (over 35%) were affected, resulting in changes of more than 15% when the samples were reanalyzed. These data indicate that the poor performance of an LC/MS/MS system could adversely affect the calculated concentrations of unknown samples even though the results for quality control samples appear to be acceptable.     

液相色谱-质谱联用法测定人血浆双氢青蒿素浓度

目的:建立液相色谱-质谱联用法测定健康人血浆中双氢青蒿素浓度的方法。方法:以青蒿素为内标,血浆样品采用液-液萃取法处理。用电喷雾离子化和正离子多离子反应监测方式检测双氢青蒿素。结果:该方法双氢青蒿素线性范围为1.01~2020 ng.ml-1;定量下限为1.001±0.072 ng.ml-1;方法回收率在93.0%~98.2%;批内、批间变异系数均<10%。结论:该方法准确、灵敏、特异、简便,适用于健康人血浆双氢青蒿素浓度的测定。